CHA2DS2-VASc Research Articles

Left atrial appendage occlusion indicated by increased thrombotic risk versus increased bleeding risk: a comparison of the stroke despite anticoagulation (STR-OAC) and EWOLUTION cohorts

Abstract Background Left atrial appendage occlusion (LAAO) provides mechanical cardioembolic protection, especially attractive for atrial fibrillation (AF) patients that cannot use oral anticoagulation therapy (OAC). Patients with prior stroke despite OAC are at high risk for recurrence and may also benefit from LAAO as (adjunctive) therapy. Purpose To investigate the efficacy of LAAO in AF patients with prior stroke on OAC compared to LAAO in AF patients with a contra-indication to OAC. Methods The STR-OAC LAAO is an international collaboration combining patients that underwent successful percutaneous LAAO because of a thrombo-embolic event or LAA thrombus on OAC from multiple LAAO registries (n=439). This cohort was compared to patients from the previously published EWOLUTION registry comprising of patients that successfully underwent LAAO because of a contra-indication for long-term OAC (n=1005). Thrombotic endpoints were prespecified and (non-procedural) major bleeding was defined as BARC score>2. Annualized event rates were calculated and compared to historical data based on individual patient risk scores. Results Both cohorts were comparable in terms of age and sex (Table 1). CHA2DS2-VASc and HAS-BLED scores were higher in the STR-OAC cohort. After LAAO indicated by a thrombotic event despite OAC, 33% of patients had a planned lifelong hybrid strategy approach of concomitant LAAO and OAC. Consequently, STR-OAC patients often continued OAC (with or without antiplatelet therapy), whereas EWOLUTION patients were more frequently discharged with antiplatelet therapy only. The annualized event rate (AER) for composite thrombotic events was slightly higher in the STROAC-LAAO compared to the EWOLUTION patients (4.2% versus 2.0%), possibly due to the higher thrombotic risk of this population. Major bleeding occurred more frequently in the EWOLUTION compared to STROAC-LAAO patients (AER 2.6% versus 1.1%, Table 2). In comparison to historically expected event rates, relative risk reduction (RRR) for thrombo-embolic events was 65% in the STR-OAC cohort, and 80% in the EWOLUTION cohort (Fig. 1). Annualized major bleeding rates were reduced with 81% and 46% in the STR-OAC-LAAO and EWOLUTION cohorts, respectively. Conclusions LAAO in AF patients with a thrombotic event despite OAC provides ischemic stroke protection similar to a guideline-recommended population with high bleeding risk. RRR for thrombotic events was more pronounced in the population contra-indicated for long-term OAC, while RRR for major bleeding was more pronounced in the patients that experienced a thrombotic event on OAC. Randomized trial data could endorse thrombotic event despite OAC as an indication for LAAO.Table 1&2Figure 1

Anticoagulation therapy in patients with atrial fibrillation and active cancer

Abstract Background Atrial fibrillation (AF) is common among cancer patients. Oral anticoagulation therapy (OAT) is important to prevent stroke in AF patients, but active cancer may also predispose to bleeding. Current knowledge on the use of OAT among AF patients with active cancer is scarce. Purpose To assess the influence of active cancer on the initiation of OAT in patients with AF and to explore cancer features predicting withholding OAT. Methods The nationwide FinACAF registry linked data from several registries covering all levels of care as well as drug purchases and included all 123 618 patients diagnosed with incident AF in Finland during 2011- 2018 with an indication for OAT (≥1 non-sex CHA2DS2-VASc point). Patients were considered to have active cancer if they had received a new cancer diagnosis or treatment for cancer during the preceding year from AF diagnosis. The primary outcome was the initiation of OAT (including non-vitamin K oral anticoagulants (NOAC) and warfarin) and the secondary outcome the initiation of any anticoagulation therapy (AAT; including OAT and low molecular-weight heparin) during the first year from AF diagnosis. Results The mean age of the patients was 73.9 (standard deviation 11.5) years and 62 955 (50.9%) of them were women. Altogether, 7015 (5.7%) patients had active cancer at AF diagnosis. The median CHA2DS2-VASc (3 [interquartile range 2-4] for both groups) and HAS-BLED (2 [interquartile range 2-3] for both groups) scores were similar in patients with active cancer and those without cancer history. Patients with active cancer, compared to those without cancer history, less often initiated OAT (47.7% vs. 70.5 %) or AAT (61.8% vs. 71.8%) (Figure). In Fine-Gray regression analyses with all-cause mortality as a competing risk, after adjusting for confounding factors, active cancer remained associated with lower likelihood of OAT (adjusted subdistribution hazard ratio (aSHR 0.501) (95% confidence interval (CI): 0.485-0.518), p<0.001) as well as AAT (aSHR 0.745 (95%-CI 0.723-0.769, p<0.001) initiation. Among cancer patients, metastases, gastrointestinal cancer and radiotherapy were associated with lower likelihood of OAT initiation, while only metastases predicted lower likelihood of AAT initiation (Table). Among patients initiating OAT, active cancer was associated with lesser likelihood of choosing a NOAC over warfarin compared to those without cancer (36.0% vs. 39.2%; adjusted hazard ratio 0.712 (95%-CI: 0.640-0.792), p<0.001). Conclusion AF patients with active cancer are less likely to initiate anticoagulation therapy, and those starting OAT are less likely to initiate with NOACs, compared to patients without cancer history. Metastases are the most important predictor of withholding anticoagulation therapy among AF patients with cancer.

Persistence to edoxaban treatment in patients with atrial fibrillation: Analysis from the Global ETNA-AF program

Abstract Background/Introduction Direct oral anticoagulants (DOACs) are now the standard treatment for stroke prevention in most patients with atrial fibrillation (AF). However, many studies have reported suboptimal adherence and persistence to DOAC treatment. Data collected in routine care, such as in the Global Edoxaban Treatment in routiNe clinical prActice (ETNA)-AF program, may provide insight into factors associated with treatment persistence. Purpose Evaluate the persistence to edoxaban treatment in a large, unselected, real-world population using 2-year data from the Global ETNA-AF study. Methods The Global ETNA-AF program is a predefined integration of prospective, observational, non-interventional regional studies from Europe, Japan, and other Asian countries to evaluate the safety and effectiveness of edoxaban in patients with AF. Demographic and clinical characteristics were collected at baseline. In this analysis, patients were stratified by persistence to edoxaban treatment during a 2-year follow-up period (ie, persistence [PERS], suspension [SUS], permanent discontinuation [PERD], and suspension with later permanent discontinuation [SUS+PERD]). Results Overall persistence was high, with 87.1% of patients under edoxaban treatment at 2 years considering both groups that discontinued edoxaban at any time (PERD and SUS+PERD). Mean patient age, creatinine clearance, CHA2DS2-VASc, and HAS-BLED score were similar between the PERS (n = 20,053), SUS (n = 3088), PERD (n = 2936), and SUS+PERD (n = 503) groups (Table). In the PERS group, there were slightly fewer patients who received previous anticoagulation (vitamin K antagonist or DOAC) and were concomitantly using anti-platelet drugs at baseline. A larger proportion of SUS+PERD vs all other patients had a history of ischaemic stroke and/or major bleeding. Overall mortality was lower in patients in the PERS and SUS groups (0.79% [95% confidence interval {CI} 0.70–0.89] and 1.85% [95% CI 1.53–2.24], respectively) compared with patients who discontinued the treatment (PERD: 22.50% [95% CI 21.12–23.98]; SUS+PERD: 13.05% [95% CI 10.73–15.88]). Notably, persistence in the Global ETNA-AF program was generally higher than reported in GLORIA-AF at 2 years (70.9%) and XANTUS at 1 year (77.4%), despite a more compromised health profile especially considering the advanced patient age. Conclusions Treatment with edoxaban in routine clinical practice is associated with high persistence (87%) at 2 years in elderly patients with AF and multiple comorbidities. Persistence to edoxaban treatment was associated with better survival during the 2-year follow-up period. Further investigation is ongoing to determine the specific causes and consequences of edoxaban suspension and discontinuation to improve personalization of thromboembolic prophylaxis in patients with AF.Table 1

One-year clinical outcomes and the impact of procedural configurations in patients with left atrial appendage occlusion

Abstract Background To evaluate the long-term clinical performance, the impact of procedural configurations and post-procedure medications in atrial fibrillation patients with percutaneous left atrial appendage occlusion (LAAO). Methods The RECORD study was a prospective, all-comers registry conducted in 39 Chinese centers that consecutively enrolling patients who received LAAO between 1st April 2019 and 31st October 2020 with minimum inclusion and exclusion criteria. Events including any death, any stroke, systemic embolism and bleeding event were collected at 1 year and adjudicated by an independent clinical event committee. Cox proportional hazard models with multivariable adjustments were applied to estimate hazard ratios (HRs) for each outcome. Results Of the 3,096 participants, 3,082 successfully received an LAAO implant and 3,013 (97.8%) completed the 1-year follow-up. Participants had a high risk of stroke (mean CHA2DS2-VASc score of 4.0) and a moderate-to-high risk of bleeding (mean HAS-BLED score of 2.4). Local anesthetic was performed in 1,287 (41.6%) patients and fluoroscopy guidance in 492 (16.0%) patients. In 1295 (42.0%) cases, one-stage combination procedures of LAAO and radiofrequency ablation or cryoablation (CA) were performed. At 1 year, the composite ischemic endpoint of death, stroke, and systemic embolism occurred in 133 (4.51%) patients. Any life-threatening, disabling or major bleeding events occurred in 71 (2.36%) patients. There was no significant association between the type of anesthesia (general versus local), modality of image guidance (TEE, ICE, or fluoroscopy) with the ischemic or bleeding events. Combination procedures of LAAO plus CA was associated with a significantly lower rate of death, stroke, or systemic embolism than performing LAAO only (3.5% versus 5.2%, HRadjusted:0.69, 95%CI:0.48-0.98, P=0.041). The commonest antithrombotic strategy was OAC | APT | APT (38.1%; corresponded to medication prescribed at discharge | 45 days | 6 months), followed by OAC | OAC | APT (27.0%). Compared with OAC | APT | APT, the OAC | OAC | APT group was associated with a higher risk of life-threatening, disabling or major bleeding (1.2% versus 2.5%, HRadjusted:0.50, 95%CI: 0.25-0.99, P=0.47); whereas the risk of death, stroke and SE was numerically similar (2.9% versus 3.0%, HRadjusted:1.05, 95%CI: 0.61-1.78, P=0.867). There was no significant difference between OAC | APT | APT and OAC+APT | APT | APT groups regarding ischemic events; however, in patients with HAS-BLED ≥ 3, OAC | APT | APT was associated with lower rates of life-threatening, disabling or major bleeding events (1.1% versus 4.8%, HRadjusted:4.55, 95%CI: 1.31-15.81, P=0.017). Conclusion In Chinese centers, patients with a WATCHMAN LAAO device had low rates of ischemic and bleeding events at 1 year. One-stage combination procedures of LAAO and catheter ablation was associated with a significantly lower rate of ischemic events than performing LAAO only.Procedural configurations to outcomesPost-LAAO antithrombotic medications

Impact of bleeding events on mortality in patients with atrial fibrillation and silent left atrial thrombi: insight from the LAT trial

Abstract Background Thrombolytic therapy is important to prevent thromboembolism in patients with atrial fibrillation (AF) and left atrial (LA) thrombi. However, bleeding complications are a major concern. Purpose To investigate the incidence and prognosis of bleeding complications in patients with AF and silent LA thrombi. Methods An analysis was performed from the LAT trial, a multicenter observational study investigating outcomes of silent LA thrombi detected by trans-esophageal echocardiography (TEE) in AF patients. Of 17,436 patients who underwent TEE, 297 (median age, 70 years; 31% female, median CHA2DS2-VASc score of 4) were eligible for inclusion. Management of oral anticoagulants was at the physician’s discretion, and the follow-up period was set as 1-year. Major bleeding was defined as intracranial hemorrhage, bleeding requiring surgery or transfusion, or ≥4 g/dl decrease in hemoglobin level. Results Prescription rates of oral-anticoagulants at baseline and the final follow-up were 81.8% and 89.9%, respectively (p = 0.002). During a median follow-up of 385 (interquartile range, 365-411) days after the thrombi detection, the incidence of thromboembolism, major bleeding, and all-cause death was 5.7% (n = 17), 11.4% (n = 34) and 8.4 % (n = 25), respectively. Patients with thromboembolism were more likely experience subsequent death than those without thromboembolism (17.7% vs. 7.9%, log-rank p = 0.063). Similarly, patients with major bleeding more frequently experienced subsequent death than those without bleeding (20.6% vs. 6.8%, log-rank p = 0.002). Time-adjusted Cox regression analysis revealed a temporal association between major bleeding and subsequent death (hazard ratio, 3.72; 95% confidence interval 1.55–8.93; p = 0.003) as well as between thromboembolism and subsequent death (hazard ratio, 2.98; 95% confidence interval 0.89–9.99; p = 0.077). Conclusions In the LAT trial, about 10% of patients with AF and silent LA thrombi experienced major bleeding during 1-year follow-up. Not only thromboembolism but also major bleeding was strongly associated with subsequent death.

Efficacy and safety of antiarrhythmic drugs for pharmacological cardioversion of atrial fibrillation depending on gender: a subanalysis of CANT II Study

Abstract Background/introduction The data on gender differences concerning antiarrhythmic drugs (AAD) applied in atrial fibrillation (AF) patients is scarce. Purpose The aim of the study was to evaluate gender differences in terms of clinical profile of AF patients, and efficacy and safety of AAD used for pharmacological cardioversion (PCV) of AF. Methods This research was a sub-analysis of retrospective multicenter Cardioversion with ANTazoline II (CANT) registry, which comprised 1365 patients with short-duration AF referred for urgent PCV with the use of AAD. Patients were categorized in terms of gender and compared in terms of clinical parameters and outcome of PCV. The primary endpoint was return of sinus rhythm within 12 hours after drug infusion and the composite safety endpoint involved bradycardia <45 bpm, hypotension, syncope or death. Results The majority of patients qualified for PCV were men (n=725, 53.1%). Females were older and more symptomatic, had higher CHA2DS2-VASc score, greater prevalence of tachyarrhythmia and higher utilization of chronic anticoagulation. The overall efficacy (71.4% vs. 70.1%,P=0.588) and safety (5.2% vs. 4.6%,P=0.603) of PCV was comparable in men and women. Amiodarone (68.3% vs. 65.9%, P=0.664) and antazoline (77.1% vs. 80.0%, P=0.19) had similar efficacy in men and women, but propafenone had lower rate of rhythm conversion in men (64.7% vs. 79.3%, P=0.046; Figure). None of the assessed AAD differed in terms of safety profile in both genders. Logistic regression showed that, among other predictors, in women the use of amiodarone vs. other AAD (odds ratio [OR] 0.569, P=0.033), while in men administration of a amiodarone (OR 0.379, P=0.001) or propafenone (OR 0.331, P=0.002) vs. other AAD were associated with lower chance of successful rhythm conversion. Conclusions Female patients with AF share different clinical profile and similar efficacy and safety of AAD used for PCV as compared to male participants. Propafenone has significantly lower efficacy in men, which requires further prospective investigation.

Metabolomics and frailty: a "from bench to bedside" approach to atrial fibrillation in older patients

Abstract Background Atrial fibrillation (AF) is the most common sustained arrhythmia diagnosed at an advanced age. The most important complications of AF are stroke, heart failure and dementia. The pathophysiology of the arrhythmia is complex and multifaceted and several aspects are still not completely understood. Purpose Our project aimed at exploring the molecular characteristics of AF in older patients using an untargeted metabolomics approach, an analytical technique that provides an insight of the global metabolic profile at an individual level. As secondary endpoints, we evaluated the association between metabolomics and acylcarnitines, which are mediators of myocyte electrical instability, and difference in metabolomics profile between healthy controls (C) and AF patients (AF-P). Method We evaluated 50 consecutive older AF-P with persistent AF, waiting to be treated with elective electrical cardioversion of the arrhythmia, and 22 healthy controls (C). In all patients, the cardiological evaluation was integrated with tools of the Geriatric Multidimensional Assessment (GMA) to describe neurocognitive function (Mini-Mental State Examination, MMSE), depressive symptoms (15-item Geriatric Depression Scale, GDS), and physical performance (Short Physical Performance Battery, SPPB). Interleukin-6 (IL-6), a marker of low-grade inflammation, was measured with ELISA assays. Metabolomics analysis and acylcarnitine measurements were carried out using gas chromatography coupled with mass spectrometry (GC-MS). Results AF-P and C did not differ by age (76 ± 6 vs. 70 ± 14 years, p = 0.055); patients had a lower proportion of women (AF-P: 32% vs. C: 64%, p = 0.012). Cluster analysis applied to metabolomic data in all population identified two subset of subjects, characterized by a different body mass index (BMI; 23.57 vs. 32.53 Kg/m², p = 0.046). When studying only the AF-P group, the simultaneous presence of a higher CHA2DS2-VASc score (4.17 ± 1.32 vs. 2.88 ± 1.83, p = 0.007), a lower physical function (SPPB; 8.97± 2.22 vs. 10.75 ± 1.13, p = 0.009), and higher IL-6 levels (4.42 vs. 2.39 pg/mL, p = 0.002) described the cluster with a worse clinical phenotype and a specific metabolomics pattern. Furthermore, an association between IL-6 and medium- long-chain acylcarnitines emerged (acylcarnitine 12:1, β = 31.7 ± 9.4, R = 0.446, p = 0.001). Conclusions Present analysis demonstrated that a specific metabolomics profile was characteristic of older AF patients with a frail phenotype, identified by higher CHA2DS2-VASc score and IL-6 concentration, and lower physical performance. Future studies are needed to reveal the single molecular pathways responsible of these behaviour, potentially useful to guide a targeted therapy. Last, inflammation per se could contribute to electrical instability in AF, while body mass index, a surrogate measure of undernutrition, could identify different metabolic pathways in controls and in patients with the arrhythmia.Metabolomics by clinical phenotypes

Sex differences in cognitive impairment and association with all-cause mortality: a report from a contemporary cohort of patients with atrial fibrillation

Abstract Background Cognitive impairment (Cogn-Imp) in patients with atrial fibrillation (AF) has been associated with adverse outcomes. The impact of sex on the association between AF and Cogn-Imp is complex and there are limited data on specific sex-differences in AF patients with Cogn-Imp and association with outcomes. Purpose To investigate the impact of sex on Cogn-Imp, as well as the association of Cogn-Imp with adverse outcomes at follow-up in a contemporary cohort of patients with AF. Methods We analyzed patients enrolled in prospective observational study of AF patients. Cognitive status was evaluated by the Mini-Mental State Examination (MMSE). Patients were stratified according to MMSE scores obtained at baseline. A MMSE score <24 was considered suggestive of Cogn-Imp. All-cause mortality was the primary outcome. Results A total of 931 AF patients were included (median age 75 [IQR 66-82], CHA2DS2VASc score median 4 [2-5], HASBLED median 1 [1-2]). Almost ninenty percent (830/910, 89.2%) of the patients were treated with oral anticoagulants (OACs). Overall, 159/931 (17.1%) of the patients had a MMSE score <24 at baseline, indicative of Cogn-Imp. Female patients had a significant higher prevalence of Cogn-Imp compared to males (22.2% vs 14.0%, p=0.001). At the multivariable logistic regression analysis (adjusted for age, hypertension, previous stroke, coronary artery disease, diabetes, CKD, PAD, heart failure, AF type and use of OACs) female sex was independently associated with Cogn-Imp (adjusted OR 1.70, 95% CI 1.13-2.57). After a median follow-up of 633 [IQR 199-1503] days, all-cause mortality was 15.6% with a significant higher prevalence in patients with Cogn-Imp vs. No-Cogn-Imp, both for males (33.3% vs 15.8%, p<0.001) and females (29.6% vs 10.5%, p<0.001). Kaplan-Meier analysis showed a lower cumulative survival of patients with Cogn-Imp vs. No-Cogn-Imp (Log Rank p=0.01, Figure). At the adjusted Cox regression analysis, Cogn-Imp was associated with an independent higher risk of all-cause mortality both in males (adjusted HR 1.99, 95% CI 1.17-3.39) and females (adjusted HR 2.03, 95% CI 1.05-3.93). Stratifying the population by age, some differences in terms of association between Cogn-Imp and all-cause mortality were evident (Table). Cognitive impairment was associated with a higher risk of all-cause mortality in female patients aged 75-84 and ≥85 years old, but among males only in patients aged 75-84. Conclusions In a prospective observational real-world cohort of AF patients, female sex was independently associated with a higher occurrence of Cogn-Imp compared to male sex. Cognitive impairment was independently associated with a higher risk of all-cause mortality in both sexes with some differences across age categories suggesting peculiar pathophysiological interactions which warrant further investigations.

Impact of atrial fibrillation on mortality and non-fatal cardiovascular outcomes in 145 293 patients admitted with COVID-19: a statewide population-linkage study

Abstract Background Atrial fibrillation (AF) is common in COVID-19 patients. The impact of AF on major-adverse-cardiovascular-events (MACE defined as all-cause mortality, myocardial infarction, ischaemic stroke, heart failure or revascularisation), recurrent admission with AF and venous thromboembolism in patients hospitalised with COVID-19 is not well-defined. Purpose This study aims to examine the impact of AF on long-term clinical outcomes including fatal and non-fatal cardiovascular outcomes in patients admitted with COVID-19. Methods Patients admitted with COVID-19 (1 January 2020 to 30 September 2021) were identified from the Admitted-Patient-Data-Collection database in New South Wales, the largest state of Australia, stratified by AF status (No-AF vs Prior-AF or New-AF during index COVID-19 admission) and followed up until 31 March 2022. A linkage look-back to year 2001 was performed to identify prior-AF history. Multivariable Cox regression was performed to assess the impact of AF status on MACE. To account for the competing risk of death and assess the impact of AF on non-fatal cardiovascular outcomes, Fine-Gray competing risk analysis was performed. Results The cohort comprised 145 293 COVID-19 patients (median age 67.4 years; 49.7% males): New-AF, n=5 140 (3.5%); Prior-AF, n=23 204 (16.0%) (Table 1). During a median follow-up of 9 months, Prior-AF and New-AF patients had significantly higher MACE rates (Prior-AF: 44.7% vs New-AF: 36.2% vs No-AF: 18.0%), including all-cause mortality (Prior-AF: 36.0% vs New-AF: 28.7% vs No-AF: 15.2%) compared to No-AF patients (both logrank P<0.001). After adjusting for age, gender, intensive-care-unit admission and Charlson comorbidity index, compared to No-AF status, New-AF and Prior-AF status were independently associated with MACE (adjusted hazard ratio[aHR]=1.17, 95% confidence interval [CI]=1.11-1.22; aHR=1.36, 95%CI=1.33-1.40 respectively; both P<0.001). Competing risk analyses showed that rehospitalisation rates for ischaemic stroke, heart failure and AF but not venous thromboembolism were significantly higher in COVID-19 patients with New-AF and Prior-AF (P<0.001) (Table 2). In a separate competing risk analysis incorporating patient’s CHA2DS2VASc status, New-AF patients had a higher rehospitalisation rate for ischaemic stroke, independent of CHA2DS2VASc group (CHA2DS2VASc=0 vs CHA2DS2VASc≥1: subdistribution HR [sHR]=3.57 and 1.61 respectively), whereas patients with Prior-AF had a higher rehospitalisation rate for ischaemic stroke only if CHA2DS2VASc≥1 (sHR=1.34) (all P<0.05). Conclusions COVID-19 patients with AF are at high risk of MACE and other adverse clinical outcomes. Such patients could be targeted for increased surveillance and additional post-discharge support. Efficacy of early anticoagulation for COVID-19 patients with new-AF to prevent stroke regardless of CHA2DS2VASc score requires further study.Table 1.Baseline characteristicsTable 2.Non-fatal CV outcomes

Sex disparities in outcomes of left atrial appendage occlusion

Abstract Background Atrial fibrillation (AF) is the most common arrhythmia in adults and is associated with an increased risk of embolic stroke. Left atrial appendage occlusion (LAAO), such as Watchman device, has demonstrated non-inferiority to anticoagulation in clinical trials for prevention of stroke in non-rheumatic AF. However, sex differences in outcomes of LAAO implantation have not been studied using a large real-world database. Purpose To identify the sex disparities in outcomes of LAAO Methods Data from the 2016-2020 National Inpatient Sample (NIS) were used to identify patients of ages ≥18 with a primary diagnosis of atrial fibrillation/flutter and a primary/secondary procedure code for LAAO. Various patient characteristics, comorbidities, and complications were also identified and compared. Propensity-matched cohorts were extracted after adjusting for multiple comorbidities and demographics. Results A total of 87,790 procedures of LAAO were performed between 2016-2020, with 58.4% males and 41.6% females. Whilst a yearly rise in the number of procedures was also observed, the trend was not statistically significant (ptrend=0.318) (Figure 1). Post-matching 6,842 males and 7,303 females were retained in our study. Females had a higher mean CHA2DS2-VASc score (4.6 vs.3.7, p<0.01) and longer length of stay than males (1.38 vs. 1.24 days, p<0.01). Furthermore, a higher incidence of cardiac tamponade (1.1% vs. 0.3%, p<0.01, aOR 3.642, 95% CI 2.231-5.946), need for mechanical ventilation (0.7% vs. 0.3%, p<0.01, aOR 1.994, 95% CI 1.168-3.401), and pericardial effusion (3.9% vs. 2.8%, p<0.01, aOR 1.359, 95% CI 1.124-1.643) were noted amongst females vs. males. Though post-procedure, females reported a higher incidence of acute kidney injury (2.2% vs. 1.9%, aOR 1.175, 95% CI 0.918-1.504, p=0.199), intra/post-operative haemorrhage (0.6% vs. 0.4%, aOR 1.635, 95% CI 0.981-2.726), and device failure (0.7% vs. 0.5%, aOR 1.118, 95% CI 0.692-1.806, p=0.650), this was not statistically significant. In addition, no differences were observed in the mean modified HAS-BLED score between the two groups (1.9 vs. 1.9, p=0.398) (Table 1). Conclusions By using a large propensity matched cohort of patients who have undergone LAAO procedure for AF, this study has demonstrated that length of stay, pericardial effusion, cardiac tamponade and need for mechanical ventilation are higher in females as compared to males. These findings necessitate the development of strategies to reduce the increased risk of adverse events for females.Figure 1

Ticagrelor or clopidogrel in atrial fibrillation patients undergoing percutaneous coronary intervention for myocardial infarction

Abstract Background Contemporary guidelines recommend clopidogrel as the P2Y12 receptor inhibitor of choice in atrial fibrillation (AF) patients with acute coronary syndrome and/or percutaneous coronary intervention (PCI) who require concomitant oral anticoagulation (OAC). Conversely, the use of ticagrelor or prasugrel in these settings is discouraged. Purpose To examine the efficacy and safety of more potent P2Y12 inhibitors (ticagrelor or prasugrel) versus clopidogrel in patients with AF on OAC undergoing PCI for myocardial infarction. Methods We conducted a Danish, nationwide, registry-based cohort study of patients on an OAC for presumed AF who underwent PCI for myocardial infarction from 2011 through 2019. Only individuals discharged on a P2Y12 inhibitor and an OAC were included, while those receiving a P2Y12 inhibitor prior to hospitalization were excluded. The primary efficacy outcome was major adverse cardiovascular events, defined as a composite of death from any cause, recurrent myocardial infarction, repeat revascularization, or stroke, while the primary safety outcome was bleeding requiring hospitalization. Death from any cause was the main secondary outcome. Absolute and relative risks for outcomes at 1 year were calculated through multivariable logistic regression with average treatment effect modeling. Efficacy outcomes were standardized for the CHA2DS2-VASc score and aspirin use while bleeding outcomes were standardized for the HAS-BLED score and proton-pump inhibitor use. Results A total of 2259 patients were included of whom 1918 (84.9%) were discharged on clopidogrel and 341 (15.1%) on ticagrelor or prasugrel (the latter two were merged into one group because only 38 persons were discharged on prasugrel). Individuals who received the more potent P2Y12 inhibitors were younger (median age 70 vs. 74 years), more often men (76.0% vs. 70.8%), and less often had prior coronary artery disease (5.6% vs. 9.6%) than those who received clopidogrel. The standardized risk of major adverse cardiovascular events was significantly lower in patients discharged on ticagrelor or prasugrel compared with clopidogrel (standardized absolute risk, 15.8% vs. 19.6%; relative risk, 0.81, 95% confidence interval [CI], 0.68 to 0.93; P=0.003), while the risk of bleeding did not differ (standardized absolute risk, 5.2% vs. 5.2%; relative risk, 1.00, 95% confidence interval, 0.69 to 1.32; P=0.99) (Figure). The risk of death was significantly lower in the group of patients who were prescribed ticagrelor or prasugrel compared with clopidogrel (P<0.001). Conclusions In patients with AF on OAC who had undergone PCI for myocardial infarction, discharge on ticagrelor or prasugrel versus clopidogrel was associated with reduced ischemic risk, but not an increased bleeding risk. While these findings appear to support an individualized choice of P2Y12 inhibitor in this population, they should be interpreted with caution given the observational nature of the study.Figure

Initiation of warfarin is associated with decreased mortality in patients with infective endocarditis: a population based cohort study

Abstract Background The use of warfarin as an anticoagulant to prevent thromboembolism in setting of infective endocarditis (IE) remains controversial due to increased bleeding risks. Purpose To study the risks of stroke, mortality and bleeding in warfarin users compared with non-use. Methods Patients aged 18 or older and diagnosed with IE in our city between January 1st 1997 and August 31st 2020 were included. Patients with use of any anticoagulant 30 days before IE diagnosis were excluded. Patients initiated on warfarin within 14 days of IE diagnosis and patients without warfarin use were matched using propensity scores (1:1 ratio). The study outcomes were ischemic stroke, all-cause mortality, intracranial hemorrhage, and gastrointestinal bleeding. Cox proportional hazards regression was used to determine the hazard ratios [95% confidence intervals (CIs)] for the predictors of study outcomes at the end of 90-day follow up. Results The matched cohort consisted of 675 warfarin users (57.0% male, age 59±16 years, mean CHA2DS2-VASc score: 1.42±1.72) and 675 warfarin non-users (53.5% male, age 61±19 years, mean CHA2DS2-VASc score: 1.58±1.76). Warfarin use was not associated with ischemic stroke risk (Hazard ratio: 1.04 [95% CI, 0.70-1.53]), but was associated with a 50% decreased risk of all-cause mortality (HR: 0.50 [0.39-0.65]). In terms of bleeding risk, intracranial hemorrhage occurred in 36 (5.3%) warfarin users and in 29 (4.3%) patients warfarin non-users, and gastrointestinal bleeding occurred in 27 (4.0%) warfarin users and in 26 (3.9%) warfarin non-users. Conclusions Warfarin use is associated with decreased risks of mortality but similar risks of ischemic stroke compared with non-use of warfarin in patients with IE.Kaplein Meier curves of study outcomes

Atrial fibrillation catheter ablation: electroporation against high-power short duration radiofrequency

Abstract Background Pulmonary vein isolation (PVI) is one of the cornerstones of rhythm-control therapy for symptomatic atrial fibrillation (AF) patients. The new ablation technologies of pulse field ablation (PFA) and high-power short-duration radiofrequency ablation (HPSD) with the new QDOT® catheter have been recently introduced in the EP lab. Aims To evaluate and compare the efficacy, and safety of single-shot PFA and HPSDRA for PVI in AF symptomatic patients. Methods Single centre, retrospective study of consecutive patients undergoing PVI with PFA or HPSD between May-December 2022. Data on demographic, procedural and clinical/ electrocardiographic recurrence (assessed after a 3-months blanking period) were analysed. Comparative analysis between both techniques was performed. Results One hundred and ten consecutive patients were included (63 ± 11 years, 75% men), with a mean CHA2DS2-VASc score of 2±1 points, median LVEF of 61% [IQR 57-62%] and a median left atrial volume index (by CT scan) of 56 mL/m2 [IQR 51-67 mL/m2]. 55% patients presented paroxysmal-AF and 19 patients (17%) performed a redo ablation. 47% (n=52) patients performed HPSD and 53% (n=58) PFA (all with CARTO®3D system v.7 and high-density mapping). In the HPSD: median RF ablation time was 792 sec [IQR 614-919sec], while in PFA was 90 sec [IQR 30-138 sec]. Median time of catheter inside the LA for PFA was 18 min [IQR 2-33 min]. Comparing HPSD and PFA (Fig 1): median procedure time was similar (91 min [IQR 71-107 min] vs 89 min [IQR 66-111 min], p=0.261), while median fluoroscopy time was lower with HPSD (5.4 min [IQR 3.1-6.8 min] vs 13.2 min [IQR 10.3-15.6 min], p<0.001); posterior wall isolation (PWI) was performed in 5 (10%) HPSD vs 21 (37%) PFA patients (p<0.001). All PFA patients undergoing PWI had first pass isolation, while only 40% of HPSD had first pass isolation. When performed PVI only, PFA presents a lower median procedure time than HPSD (76 min [IQR 62-93 min] vs 97 min [IQR 69-135 min], p=0.048). There was only one major complication, a cardiac tamponade with PFA, treated with pericardiocentesis. At 3 months of follow-up, 17% (n=10) patients had clinical or electrocardiographic AF recurrence: 7 PFA patients and 3 HPSD patients (p=0.127). Conclusions PFA and HPSD were both feasible and safe. When undergoing PVI-only, procedure time was lower with PFA. In patients undergoing PWI, PFA achieved higher first pass isolation. Although still in its early real-world evaluation, both techniques seem to be efficient, providing low AF recurrence during follow-up.

Atrial fibrillation burden and timing of anticoagulation therapy in patients with screen-detected and clinically-diagnosed AF

Abstract Purpose We evaluated the impact of atrial fibrillation (AF) burden and timing of oral anticoagulation (OAC) therapy initiation on stroke risk in patients with screen-detected and clinically-diagnosed AF. Methods Consecutive patients aged ≥65 years attending medical outpatient clinics with or without known AF were prospectively enrolled for AF-screening using handheld single-lead ECG (AliveCor) from 12/2014 to 12/2017 (NCT02409654). Repeated screening was performed in patients with >1 visit during this period. Patients who participated in repeat screening were included in final analysis. Patients with previously known AF who were in AF in the initial screening and those with repeat screen-positivity were considered probably persistent AF, otherwise paroxysmal AF (single screen-positivity) or no AF (never screen-positive). Time from AF detection to initiation of OAC (Dx-to-Rx) was divided into two exposure levels, Dx-to-Rx ≤ 1 and >1 month. Ischemic stroke risk was estimated using adjusted sub-distribution hazard ratios (aSHR) derived from Fine and Gray regression models, accounting for death as competing risk, adjusting for components of CHA2DS2VASC score and chronic renal disease, with no AF as reference and stratified according to AF burden and Dx-to-Rx. Results Of 11,972 patients enrolled, 3,853(32.2%) received repeated screening (mean age 76.7±7.3, female 47.5%), of which 3.7% (n=144) had screened-detected AF, 25.2% (n=972) previously known AF, 5.9% (n=226) clinically-diagnosed AF during follow-up, and 65.2% (n=2,511) no AF. Persistent AF was identified in 16.7% (n=644/3,853). Of patients with all AF categories, 55.1% (n=739/1,342) initiated OAC within 1 month after AF diagnosis. During a median follow-up period of 7.2(IQR: 6.1-7.5) years, compared to no AF, patients with paroxysmal AF and Dx-to-Rx ≤ 1m (aSHR=1.40, 95%CI:0.80-2.47) had similar low risk of ischemic stroke, while aSHR was highest for persistent AF and Dx-to-Rx >1m (aSHR=2.42, 95%CI:1.38-4.26), followed by persistent AF with Dx-to-Rx≤ 1m (aSHR=2.19,95%:1.47-3.28), and paroxysmal AF with Dx-to-Rx >1m (aSHR=2.00,95%CI:1.32-3.02) (Figure). Subgroup analysis revealed the effect of early initiation of OAC (P for interaction=0.936) and higher AF burden (P for interaction=0. 863) were consistent across screen-detected and clinically-diagnosed AF. Conclusion Among patients with screen-detected AF or clinically-diagnosed AF, lower AF burden and immediate initiation of OAC therapy were associated with reduction in risk of ischemic stroke. Early detection of AF by screening facilitating early OAC prophylaxis might improve clinical outcomes.Cumulative risk of ischemic stroke

Healthcare resource utilisation and safety outcomes in patients undergoing transcatheter mitral valve repair - A nationwide analysis

Abstract Background Since the publication of the EVEREST II, MITRA-FR and COAPT trials, the domain of transcatheter edge-to-edge repair (TEER) for mitral regurgitation has been rapidly progressing. However, real-world data on peri-procedural outcomes are still limited. Purpose To analyse outcomes of peri-procedural healthcare resource utilisation and in-hospital safety after TEER between 2016 and 2019 in the United States. Methods The US National Inpatient Sample was utilised to identify adult patients undergoing TEER. Primary outcomes (hospital resource utilisation) were hospital length of stay (LOS), hospital costs and adverse discharge disposition to a nursing or rehabilitation facility. Secondary outcomes (safety) were in-hospital mortality, post-procedural bleedings, vascular complications, ischemic strokes, cardiogenic shocks, cardiac arrests and pericardial tamponades. Multivariable regression models were used to analyse outcomes. Results 4,020 adult patients undergoing a TEER procedure were included. The included population was relatively frail: average age of 78.1 years (±9.7), average Charlson Comorbidity Index of 3 [IQR 1-4], average number of cardiovascular risk factors of 3 [2-4] per patient, average CHA2DS2-VASc score of 4 [3-5] and average simplified HAS-BLED score of 2 [2-3]. Distribution of the procedure was balanced between both sexes: 2,159 (53.7%) males vs. 1,861 (46.3%) females. Procedures were predominantly performed in large hospitals with 3,052 cases (75.9%), as well as in regional "hubs" at both US coastal regions with 543 cases (13.5%) in the Middle Atlantic region, 832 cases (20.7%) in the South Atlantic region, 535 cases (13.3%) in the East North Central region and 690 cases (17.2%) in the Pacific region. TEER procedure showed relatively save outcomes: 34 in-hospital deaths (0.8%), 119 (3.0%) post-procedural bleedings, 1 vascular complication requiring surgery, 24 (0.6%) ischemic strokes, 64 (1.6%) cardiogenic shocks, 20 (0.5%) cardiac arrests and 13 (0.3%) pericardial tamponades. Between 2016 and 2019, hospital LOS decreased by 22% [95% Confidence Interval (CI) 0.73-0.83], hospital costs by 6% [95% CI 0.90-0.98] and post-procedural discharge rates to a nursing or rehabilitation facility by 40% [95% CI 0.41-0.88]; each P<0.001 (Figure). Post-procedural bleedings and cardiac arrests were reduced by 55% [95% CI 0.27-0.76] and 87% [95% CI 0.02-0.61] during the study period, respectively. In-hospital mortality, ischemic stroke, cardiogenic shock and pericardial tamponade decreased numerically but were not statistically significant (due to low overall event rates). Of note, there was a linear increase in all adverse outcomes with increasing patient comorbidity level (P for trend <0.001), particularly in patients with atrial fibrillation or flutter. Conclusion TEER procedure has become a safer and more efficient procedure. Careful considerations should be taken when performing the procedure in patients with multiple comorbidities.

Is pre-diabetes a predictor of events in patients with atrial fibrillation?

Abstract Introduction Diabetes mellitus (DM) not only increases the probability of presenting atrial fibrillation (AF), but it is also a predictor of ischemic stroke included in scales such as CHA2DS2VASc. However, there is limited information on the association between glycated hemoglobin (HbA1c) levels and ischemic, embolic or hemorrhagic events in patients with pre-diabetes and AF. Objectives This study aimed to investigate whether the presence of pre-diabetes in patients with AF increases the risk of ischemic events, hemorrhagic events, myocardial infarction or death. Methods We used data from the CardioCHUVI-AF registry, which included 18,285 patients with AF from a Galician health area between January 2014 and December 2019. Patients with valvular AF (n=376), with loss of follow-up (n=97), without information on baseline characteristics (n=48) and without data on HbA1c (12,473) were excluded. The final cohort consisted of 5,291 patients, 2,993 were non-diabetics (56.6%) and 2,298 with known diabetes (43.4%). This final cohort was classified according to HbA1c in diabetics if HbA1c is more than 6.5% (n= 1,546; 29.2%), pre-diabetics when HbA1c is between 5.7 and 6.4% (n =2,233; 42.2%) and non-diabetics if HbA1c was less than 5.7% (n = 1,512; 28.6%). Competing hazards regression analysis for non-fatal events (with death as the competing event) and conventional Cox regression for mortality were performed. Results 2,993 non-diabetic patients with AF and HbA1c data were followed for 4.1 ± 1.6 years. The mean age was 73.0 ± 9.9 years, 47.4% were women, the mean CHA2DS2VASc score was 2.9 ± 1.4 points, the mean HASBLED score was 2.5 ± 1.2 points, and 2,407 (80.4%) patients were under treatment with oral anticoagulants. In the Kaplan Meier curves, no was observed a higher rate of events in pre-diabetes patients in comparison with patients with normal glycemia. In the multivariate analysis, after adjusting for the CHA2DS2VASc and HASBLED scales, as well as for anticoagulant therapy, it was observed that pre-diabetes was not associated with an increased risk of mortality ( HR= 0.80; 95% CI, 0.60-1.08), ischemic stroke (HR= 0.99; 95% CI, 0.71-1.38), major hemorrhage (HR= 0.78; 95% CI, 0.60-1.02) or myocardial infarction (HR= 1.08; 95% CI, 0.65-1.79), compared with patients with normal glycemia. Conclusions In our registry, non-diabetic patients with atrial fibrillation do not have a higher risk of events when their glycated hemoglobin is in the pre-diabetes range.

Fully automatic screening for atrial fibrillation using a photoplethysmography based wristband and a novel smart infrastructure

Abstract Background Atrial Fibrillation (AF) is the leading cause of stroke, and its prevalence is expected to rise. While early detection is crucial in preventing thromboembolic events, its often asymptomatic and paroxysmal nature makes it challenging to capture using conventional electrocardiography (ECG). Photoplethysmography (PPG) enabled devices, such as smartwatches, allow continuous monitoring of the heart rhythm and accurate screening for AF. Purpose In this study, we aimed to build an IT-infrastructure for fully automated screening of AF in hospitalised patients at risk using a PPG-based wrist worn wearable device. Methods We conducted an investigator-initiated, prospective, clinical trial to evaluate the performance of a PPG-based wristband coupled to an automatic data process device hub in hospitalised patients. Participants with a CHA2DS2-VASc score of two or higher and no prior history of AF were eligible for the study. Consenting participants received a wristband with a built-in PPG sensor to be worn during the entire hospital stay. Data from the wristband was automatically transmitted, stored, analysed and visualised. When absolute arrhythmia (AA) was detected in the PPG signal, a subsequent seven-day Holter ECG was performed to confirm the diagnosis. Results A total of 346 patients were included in the analysis (age 72 ± 10 years; 175 females (50.6%); mean CHA2DS2-VASc score of 3.5 ± 1.3). No data was lost in the process. The mean monitoring time was 4.3 ± 4.4 days, 45.9% was evaluable. In twelve patients (3.5%, CI: 1.5% - 5.4%) absolute arrhythmia (AA) was detected in the PPG-signal. The mean screening time until first detection of AA was 14.7 ± 16.8 hours. The highest detection rate was observed within the first 24 hours of screening (p = 0.004) (Figure 1). The AA burden per hour was 1.9 times greater during the night (22:00 - 06:00) compared to the day (p = 0.003) (Figure 2). Of the 346 patients, 304 (87.9%) were compliant in wearing the wristband for the entire hospitalisation. In nine patients a Holter ECG was recorded, no AF was identified. Conclusions We successfully established an infrastructure for automated AF screening in hospitalised patients using wrist-worn PPG devices, enabling real-time visualisation of incoming data and facilitating therapeutic interventions with minimal delay. To our knowledge this is the first hospital to implement a fully automated AF screening infrastructure based on PPG devices. In a population at risk, AA was identified in 3.5% of all patients. The high compliance rate of the wearable device further supports its feasibility and utility in clinical practice.Figure 1:Time to first detection of AAFigure 2:Total AA burden per hour

Clinical characteristics of apixaban prescription in AF patients with single dose-reduction criterion: ASPIRE (efficacy and safety of apixaban in real-world practice in Korean frail patients with AF)

Abstract Background/Introduction Previous observational studies reported that off-label underdosed apixaban might be associated with a higher risk of stroke. However, the real-world clinical practice data on the off-label underdosed apixaban in patients with atrial fibrillation (AF) who meet single dose reduction criteria remains scarce. Purpose This study aimed to evaluate the apixaban dosing pattern in patients with AF who met a single dose reduction criterion. The difference in clinical characteristics underlying the on-label and off-label underdose prescription of apixaban was also assessed. Methods The efficAcy and Safety of aPixaban In REal-world practice in Korean frail patients with AF (ASPIRE) study is a multicenter, prospective cohort study. This study included patients with AF having a single dose reduction criterion of apixaban. Study subjects were categorized into two groups according to apixaban dose (on-label 5 mg twice daily [on-label], or off-label underdose 2.5 mg twice daily [off-label]). We evaluated the difference in the clinical characteristics were evaluated. Additionally, the ‘marginal zone’ was defined as age between 75 and 80 years, weight between 60 and 65kg, and creatinine level between 1.2-1.5mg/dL. Results A total of 1997 patients were included in this analysis (mean age 74.3±7.8 years, women 55.8%); 591 (29.7%) patients were 80 years or older, 1250 (62.6%) patients had body weight 60 kg or below, and 156 (7.8%) patients had serum creatinine 1.5mg/dL or higher. Of these patients, 1022 (51.2%) patients were prescribed off-label underdose apixaban. The off-label group was older and had higher mean CHA2DS2-VASC score, Charlson Comorbidity Index, and HAS-BLED scores than the on-label group. Hypertension, heart failure, prior bleeding history, chronic kidney disease, anemia, and concomitant antiplatelet agent usage were more prevalent in the off-label group, but prior stroke history was more common in on-label group. In the age ≥ 80 years group, the marginal zone serum creatinine was more prevalent in off-label group (p=0.011). In the body weight ≤ 60 kg group, the prevalence of marginal zone bodyweight and serum creatinine were higher in off-label group (p<0.001 and p=0.02, respectively). In creatinine ≥ 1.5 mg/dL group, the proportion of marginal zone body weight were more common in off-label underdose group (p=0.001) (Figure). Conclusions Among AF patients with a single dose reduction criterion for apixaban, almost half of the patients were prescribed off-label underdose apixaban. Physicians were more likely to prescribe off-label underdose apixaban in patients with more frail characteristics, whereas on-label apixaban was preferred in patients with prior history of stroke. The clinical outcome of off-label underdose apixaban would be compared with the on-label standard dose in a future study.

Same day discharge after interventional electrophysiology procedures, first German experience

Abstract Background and purpose In most European countries, the current postprocedural gold standard following electrophysiological (EP) interventions implies the overnight monitoring of the patients in the hospital. Due to limited healthcare capacities and an increasing safety profile of ablation procedures, the mandatory overnight monitoring is under debate. Same day discharge protocol (SDD) ablation might be a safe and efficient alternative. We present the first German experience on SDD for EP interventions. Methods Patients receiving interventional EP procedures with a maximum of two VAs were discharged on the day of procedure, after the hemostasis and ambulation were proven. The VA hemostasis was achieved either by using a vascular closure system (VCS) or by a figure-of-eight suture followed by compressive bandage application. All patients were scheduled for a medical visit the day after procedure for groin examination and suture removal. Results A total of 12 patients (25% females, median age 64 (57.3, 66.8) years, median BMI 30.5 (22.3, 33.7) Kg/m2) undergoing EP procedures followed the SDD protocol in our center. All patients had an atrial fibrillation (AF) diagnosis, 66.7% of them paroxysmal. Five (45.5%) patients had a CHA2DS2VASc score of 1. A total of 4 (33.3%) patients presented arterial hypertension, 3 (25%) diabetes mellitus, 1 a history of stroke, 1 of myocardial infarction and 1 had chronic kidney disease and kidney transplantation. Eleven (91.7%) patients were under oral anticoagulation. The most common procedure was AF ablation, in 10 (83.3%) patients, while 1 (8.3%) patient underwent cavotricuspid isthmus (CTI) ablation and 1 (8.3%) a left atrial appendage closure procedure. In 10 (72.7%) AF ablations the energy source was cryoenergy, in 1 laserenergy and in 1 electroporation. The CTI ablation was performed by means of radiofrequency. A VCS was used in 7 (58.3%) patients. Six of these patients received 2 VCSs, while the patient with PFA based ablation had a single vascular access, thus only one VCS. The procedure was reported successful in all cases, and no intraprocedural complication occurred. During the next day visit, a groin hematoma has reported in 2 (16.7%) patients, no one requiring further therapeutical measures or hospitalization. All the other patients had no puncture related complications. The median FU time was 46.5 (26, 90.3) days. During FU only one patient had an unplanned ambulatory visit due to flecainide intolerance. Readmission during FU was reported in only 2 patients, none of them procedure related. Conclusions In selected patients undergoing EP procedures SDD seems to be safe and feasible. This approach increases healthcare capabilities, patients' comfort and reduces the cost of medical care.

External validation of the new REACT-HF score for heart failure prediction in patients with atrial fibrillation

Abstract Background Heart failure (HF) represents the main cause of hospital admissions and deaths among atrial fibrillation (AF) patients, but precise risk prediction tools are lacking. Recently, the REACT-HF score has been developed to predict incident HF hospitalizations or cardiovascular (CV) death within 2-years based on 12 variables (sex, age, height, creatinine clearance, diabetes, vascular disease, valvular heart disease, heart rate and rhythm, left ventricular hypertrophy and intraventricular conduction delay). Purpose The aim of the present study was to externally validate the REACT-HF score within the Swiss-AF and BEAT-AF cohorts, and to investigate whether this score model can be improved by adding biomarkers (hs-CRP, NT-proBNP, hs-TNT). Methods We included 2’599 AF patients from the Swiss- and BEAT-AF cohorts without prior history of HF, with at least one follow-up and with all baseline variables needed for the REACT-HF score. To validate the score, we estimated a Cox model with the original score as the only predictor. We further explored whether the predictive performance of the REACT-HF score model could be improved by adding any combination of the above listed biomarkers. The primary outcome was incident HF hospitalization or CV death. Secondary outcomes included the individual components of the primary outcome and all-cause mortality. Results Mean age was 70.2 years, 29.1% were female and 54.8% had paroxysmal AF. The mean CHA2DS2-VASc score was 2.7 (+/- 1.6). The most frequent comorbidities were hypertension (65%), diabetes (12%), vascular disease (23%) and coronary artery disease (36%). Most patients (1’883) presented a very low REACT-HF score below 0.05 (72.4%), 530 patients between 0.05 and below 0.1 (20.4%) and 186 had a risk score of 0.1 and above (7.2%). In the validation set, 380 (14.6%), 471 (18.1%), 511 (19.7%) 561 (21.6%) and 676 (26.0%) patients were categorized in the lowest to the highest quintiles based on the original score`s quintiles. Figure 1 shows the Kaplan-Meier survival curves for the primary endpoint of first HF hospitalization or CV death by quintiles of the REACT-HF score, applied in our pooled cohort. And Figure 2 shows the Kaplan-Meier curves for the 1st HF hospitalization. The incidence rates at 2-year follow-up per 100 patient-years of the primary outcome (0.39, 0.59, 1.58, 3.97, 7.53), HF hospitalization (0.39, 0.49, 1.38, 2.75, 6.26), CV death (0.0, 0.10, 0.20, 1.29, 2.12), and all cause-death (0.10, 0.49, 0.78, 2.29, 4.24) all increased gradually among the quintiles of risk score. The estimated c-statistic for the composite primary outcome was 0.764 (approximate 95% CI, 0.723-0.806). The best biomarker enhanced-model within our cohort was the model including hs-CRP and NT-proBNP (c-statistic 0.810). Conclusions The REACT-HF score discriminates well for prediction of HF hospitalization and CV death in a contemporary AF population and can be improved by including NT-pro-BNP and hs-CRP.